The study was conducted on people who were taking their first anti-HIV drug regimen (including an Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI), a type of anti-HIV drug) but the drugs in this regimen were not doing a good job of fighting their HIV infection.

The main purpose of this study was to compare two other anti-HIV drug regimens to see how well they fight HIV. The study also looked at how well participants tolerate the drug regimens and how safe they are.

The study was designed to determine whether taking the combination of lopinavir/ritonavir (LPV/r) plus raltegravir (RAL) works as well as what is usually used for second-line therapy: LPV/r plus the best-available nucleoside (nucleotide) reverse transcriptase inhibitor (NRTI) combination. Testing a regimen that does not include any NRTIs was important because NRTIs may no longer work for patients who received them as part of their first treatment regimen.

The primary endpoint was time to virologic failure. Virologic failure was defined as confirmed viral load >400 copies/mL at or after week 24. The Kaplan-Meier estimate of the cumulative probability of virologic failure by week 48 was used.

Number of Participants With HIV-1 Drug Resistance Mutations in Protease, Reverse Transcriptase, and Integrase in Participants With Virologic Failure at Baseline and at Time of Virologic Failure [ Time Frame: From study entry through to week 96 ] [ Designated as safety issue: No ]

Mutations were defined as major IAS mutations in the IAS-USA July 2014 list. New mutations were those detected at virologic failure but not at baseline.

Number of Participants With Grade 3 or Higher Adverse Event (AE) at Least One Grade Higher Than Baseline [ Time Frame: From start of randomized treatment to off randomized treatment (up to 96 weeks) ] [ Designated as safety issue: Yes ]

The DAIDS Adverse Event (AE) Grading Table, Version 1.0, December 2004 (Clarification, August 2009) was used for grading of AEs.

Number of Participants Discontinuing Randomized Treatment for Toxicity [ Time Frame: From Start of Randomized Treatment to Off Randomized Treatment (up to 96 weeks) ] [ Designated as safety issue: Yes ]

Discontinuation of randomized treatment for toxicity included participant decision to discontinue for low grade toxicity. Within class NRTI changes were not considered discontinuations.

Number of Participants With a New AIDS-defining Events or Death [ Time Frame: From study entry throughout follow-up (up to 96 weeks) ] [ Designated as safety issue: No ]

AIDS-defining events were those recognized by the Centers for Disease Control (CDC) and World Health Organization (WHO)

Number of Participants With a Targeted Serious Non-AIDS-defining Event or Death [ Time Frame: From study entry throughout follow-up (up to 96 weeks) ] [ Designated as safety issue: No ]

Certain laboratory values obtained within 45 days prior to study entry. More information on this criterion can be found in the study protocol.

Negative pregnancy test within 48 hours prior to study entry.

Must refrain from participating in a conception process, and, if participating in sexual activity that could lead to pregnancy, must use at least one acceptable type of contraceptive. More information on this criterion can be found in the study protocol.

Ability and willingness of participant or legal guardian/representative to provide informed consent.

No intention to relocate away from current geographical area of residence for the duration of study participation.

Exclusion Criteria:

Use of any immunomodulator, HIV vaccine, or other investigational therapy within 45 days prior to study entry, with the exception of a tapering course of corticosteroids as acute therapy for pneumocystis jiroveci pneumonia (PCP) or acute asthma/chronic obstructive pulmonary disease flare and/or prednisone at a daily dose of <10 mg (physiologic replacement dose).

If the potential participant has had resistance testing, evidence of broad NRTI cross-resistance that, in the opinion of the investigator, would not allow selection of an effective NRTI combination if the participant were randomized to the LPV/r + best available NRTIs arm.

Prior exposure to a Protease Inhibitor.

Known history of congenital long QT syndrome, hypokalemia, or planned use of other drugs that prolong the QT interval.

Pregnancy or breast-feeding.

Known history of chronic hepatitis B virus (HBV) infection or current HBV infection defined by the presence of hepatitis B surface antigen in serum or plasma.

Requirement for taking any medications that are prohibited with the study drugs. More information on this criterion can be found in the study protocol, section 5.4.

Known allergy/sensitivity or any hypersensitivity to components of study drugs or their formulation.

Active drug or alcohol use or dependence or other condition that, in the opinion of the site investigator, would interfere with adherence to study requirements.

Serious illness requiring systemic treatment and/or hospitalization until candidate either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01352715

Locations

Brazil

Instituto de Pesquisa Clinica Evandro Chagas (12101)

Rio de Janeiro, Brazil, 21045

India

BJ Medical College CRS (31441)

Pune, Maharashtra, India, 411001

NARI Pune CRS

Pune, Maharashtra, India

Y.R.G Ctr, for AIDS Research and Education (11701)

Chennai, India

Kenya

AMPATH at Moi Univ. Teaching Hosp. Eldoret CRS (12601)

Eldoret, Kenya, 30100

Malawi

College of Med. JHU CRS (30301)

Blantyre, Malawi

University of North Carolina Lilongwe CRS (12001)

Lilongwe, Malawi

Peru

San Miguel CRS

San Miguel, Lima, Peru

Barranco CRS (11301)

Lima, Peru, 18 PE

South Africa

Wits HIV CRS (11101)

Johannesburg, Gauteng, South Africa

Durban Adult HIV CRS (11201)

Durban, South Africa, 4013 SF

Soweto ACTG CRS (12301)

Johannesburg, South Africa

Univ. of Witwatersrand CRS (11101)

Johannesburg, South Africa

Tanzania

Kilimanjaro Christian Medical CRS

Kilimanjaro Region, Moshi, Tanzania

Thailand

Chiang Mai University ACTG CRS (11501)

Chiang Mai, Thailand, 50202

Zimbabwe

UZ-Parirenyatwa CRS (30313)

Harare, Zimbabwe

Sponsors and Collaborators

AIDS Clinical Trials Group

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:

Alberto M La Rosa, MD

Asociacion Civil Impacta Salud y Educacion - Miraflores, CRS

Study Chair:

Ann C Collier, MD

Univ. of Washington Clinical HIV Research Program (CHIRP)

More Information

Publications:

[1] Hull M, Moore D, Harris M, et al. A lamivudine (3TC)-based backbone in conjunction with a boosted protease inhibitor (PI) is sufficient to achieve virologic suppression in the presence of M184V mutations. Program and abstracts of the 49th Interscience Conference on Antimicrobial Agents and Chemotherapy; September 12-15, 2009; San Francisco, California. Abstract H-916.